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1.
Protein Pept Lett ; 29(5): 473-484, 2022.
Article in English | MEDLINE | ID: mdl-35306981

ABSTRACT

AIM: This study aims to identify novel post-translational modifications in human serum albumin by mass spectrometry. BACKGROUND: Serum albumin is the most abundant protein in plasma, has many physiological functions, and is in contact with most of the cells and tissues of the human body. Post-translational modifications (PTMs) may affect functions, stability, and localization of albumin. METHODS: Human serum albumin (HSA) was used for tryptic digestion in-solution or in-gel. Mass spectrometry was applied to identify PTMs in HSA. 3-dimensional modeling was applied to explore the potential impact of PTMs on known functions of albumin. RESULTS: Here, we report the identification of 61 novel PTMs of human serum albumin. Phosphorylation, glycosylation, nitrosylation, deamidation, methylation, acetylation, palmitoylation, geranylation, and farnesylation are some examples of the identified PTMs. Mass spectrometry was used for the identification of PTMs in a purified HSA and HSA from the human plasma. Threedimensional modeling of albumin with selected PTMs showed the location of these PTMs in the regions involved in albumin interactions with drugs, metals, and fatty acids. The location of PTMs in these regions may modify the binding capacity of albumin. CONCLUSION: This report adds 61 novel PTMs to the catalog of human albumin.


Subject(s)
Protein Processing, Post-Translational , Serum Albumin, Human , Acetylation , Humans , Mass Spectrometry/methods , Phosphorylation , Serum Albumin/metabolism , Serum Albumin, Human/chemistry
2.
Curr Protein Pept Sci ; 23(2): 114-120, 2022.
Article in English | MEDLINE | ID: mdl-35176988

ABSTRACT

Post-translational modifications (PTMs) may affect the functions of human serum albumin. Here we review reports of novel PTMs of human serum albumin. This study reviewed one hundred twenty-three recently reported novel O-phosphorylation, glycation, methylation, carbonylation, and acetylation of albumin. Furthermore, the potential impact of these PTMs on albumin functions is discussed. Knowledge of these PTMs of albumin is important for the use of albumin in medical applications, e.g., in transfusion, drug formulations, and remedies.


Subject(s)
Protein Processing, Post-Translational , Serum Albumin, Human , Acetylation , Humans , Methylation , Phosphorylation
3.
EJIFCC ; 33(4): 295-308, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36605305

ABSTRACT

Purpose: Serum albumin is in contact with practically all cells in the human body, including tumor cells in cancer patients. The purpose of this study was to explore whether cancer cells affect post-translational modifications (PTMs) of albumin. Material and methods: Mass spectrometry was used to identify the PTMs. Purified human serum albumin was incubated with human breast cancer cells MDA-MB-231, MDA-MB-468, MCF7, or kept in water or in cell culture media. PTMs which were affected upon exposure of the albumin to cancer cells were identified. Three-dimensional analysis was performed to locate PTMs in albumin. Results: We report here that an exposure to human breast cancer cells affected post-translational modifications (PTMs) of 14 peptides of human serum albumin (HSA). PTMs at 8 peptides were observed upon exposure of HSA to metastatic MDA-MB-231 and MDA-MB-468 breast cancer cells. PTMs at another 6 peptides were lost in MDA-MB-231 and MDA-MB-468 cells, while these 6 PTMs were observed in HSA exposed to conditionally tumorigenic MCF7 cells, or in HSA kept in water or a cell culture medium. Cancer cell altered phosphorylation, deamidation followed by methylation, acetylation, myristylation, palmitoylation, methylation, cysteine persulfide, and S-6-FMN cysteine modifications were detected in HSA. These PTMs locate predominantly in IB and IIA domains of HSA. Three-dimensional analysis showed that this region corresponds to the lipid-binding site and Sudlow's site 1. Conclusion: Data reported here show that 14 PTMs of human serum albumin can be modified upon its exposure to human breast cancer cells.

4.
J Inflamm Res ; 14: 5349-5365, 2021.
Article in English | MEDLINE | ID: mdl-34703273

ABSTRACT

Cardiac remodeling is the process by which the heart adapts to stressful stimuli, such as hypertension and ischemia/reperfusion; it ultimately leads to heart failure upon long-term exposure. Autophagy, a cellular catabolic process that was originally considered as a mechanism of cell death in response to detrimental stimuli, is thought to be one of the main mechanisms that controls cardiac remodeling and induces heart failure. Dysregulation of the adipokines leptin and adiponectin, which plays essential roles in lipid and glucose metabolism, and in the pathophysiology of the neuroendocrine and cardiovascular systems, has been shown to affect the autophagic response in the heart and to contribute to accelerate cardiac remodeling. The obesity-associated protein leptin is a pro-inflammatory, tumor-promoting adipocytokine whose elevated levels in obesity are associated with acute cardiovascular events, and obesity-related hypertension. Adiponectin exerts anti-inflammatory and anti-tumor effects, and its reduced levels in obesity correlate with the pathogenesis of obesity-associated cardiovascular diseases. Leptin- and adiponectin-induced changes in autophagic flux have been linked to cardiac remodeling and heart failure. In this review, we describe the different molecular mechanisms of hyperleptinemia- and hypoadiponectinemia-mediated pathogenesis of cardiac remodeling and the involvement of autophagy in this process. A better understanding of the roles of leptin, adiponectin, and autophagy in cardiac functions and remodeling, and the exact signal transduction pathways by which they contribute to cardiac diseases may well lead to discovery of new therapeutic agents for the treatment of cardiovascular remodeling.

5.
Biochem Biophys Res Commun ; 521(4): 1010-1016, 2020 01 22.
Article in English | MEDLINE | ID: mdl-31727370

ABSTRACT

Smad2 is a crucial component of intracellular signaling by transforming growth factor-ß (TGFß). Here we describe that Smad2 is glycosylated, which is a novel for Smad2 post-translational modification. We showed that the Smad2 glycosylation was inhibited upon treatment of cells with 17ß-estradiol, and was enhanced in cells in a dense culture as compared to cells in a sparse culture. The Smad2 glycosylation was not dependent on the C-terminal phosphorylation of Smad2, and was not affected by TGFß1 treatment of the cells. Smad2 was glycosylated at multiple sites, and one of the predicted sites is Serine110. Thus, Smad2 is glycosylated, and this post-translational modification was modulated by 17ß-estradiol but not by TGFß1.


Subject(s)
Protein Processing, Post-Translational , Smad2 Protein/metabolism , Transforming Growth Factor beta1/metabolism , Alanine/genetics , Animals , CHO Cells , Cell Count , Cell Nucleus/drug effects , Cell Nucleus/metabolism , Concanavalin A/pharmacology , Cricetinae , Cricetulus , Estradiol/pharmacology , Glycosylation , Humans , Lectins/pharmacology , MCF-7 Cells , Mutation/genetics , Plant Lectins/pharmacology , Protein Processing, Post-Translational/drug effects , Protein Transport/drug effects , Serine/genetics
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